Regarding HIV-1 entry, replication, and the roles of viral enzymes, all of the following are true EXCEPT:

Explanation

## HIV-1 Entry, Replication, and Enzyme Functions ### Correct Mechanisms #### CD4 and Coreceptor Binding **Key Point:** HIV-1 entry is a two-step process: 1. **gp120 binds CD4** → conformational change exposes the coreceptor binding site 2. **Coreceptor binding** (CCR5 or CXCR4) → further conformational changes expose gp41 3. **gp41 mediates fusion** → viral and cellular membranes merge **High-Yield:** CCR5-tropic (R5) viruses predominate early in infection; CXCR4-tropic (X4) viruses emerge later and correlate with CD4 decline and disease progression. #### Integrase Function **Clinical Pearl:** Integrase catalyzes: - 3' processing of viral DNA ends - Strand transfer into host chromosome - Host cell DNA repair machinery seals the gaps The integrated provirus becomes a **permanent genetic element** — this is why HIV establishes chronic infection and why cure requires eliminating all infected cells. #### Protease Function **Mnemonic:** **PROTEASE = PRO-TE-ASE** — **PRO**duces **TE**rminal **A**ctive **SE**quences. Protease cleaves: - **gag** → p24, p17, p7 (structural proteins) - **gag-pol** → RT, integrase, protease (enzymes) - **env** → gp120, gp41 (envelope proteins) **Warning:** Immature, uncleaved particles are **non-infectious**. Protease inhibitors (PIs) prevent maturation, producing defective virions — a key mechanism of antiretroviral therapy. ### The Critical Error: Reverse Transcriptase Independence **High-Yield:** Option 4 claims RT works "independent of host cell machinery" and "does not require nucleotide precursors from the host." This is **COMPLETELY FALSE**. #### Why RT Depends on Host Machinery | Requirement | Source | Explanation | |-------------|--------|-------------| | **dNTP precursors** | Host cell | RT polymerizes dNTPs (dATP, dGTP, dCTP, dTTP) — these must come from the host | | **RNA template** | Viral genome | The viral RNA is the template, but degradation products are recycled | | **Primer** | Host tRNA^Lys^ | Cellular tRNA binds the viral RNA to initiate reverse transcription | | **Location** | Host cytoplasm/nucleus | RT operates within the infected cell environment | | **Energy (ATP/GTP)** | Host cell | Nucleotide triphosphates power polymerization | **Clinical Pearl:** This dependence on host dNTP pools is why: - **NRTIs** (nucleoside RT inhibitors) work — they are analogs that terminate DNA chain elongation - **NNRTIs** (non-nucleoside RT inhibitors) work — they bind the RT active site and block catalysis - Cells with high dNTP pools (activated T cells, macrophages) are more permissive to HIV replication ### Integration of Entry, Replication, and Enzyme Roles ```mermaid flowchart TD A["HIV-1 virion approaches target cell"]:::outcome --> B["gp120 binds CD4"]:::action B --> C{"Coreceptor available?"}:::decision C -->|"CCR5 or CXCR4"| D["gp41 mediates fusion"]:::action D --> E["Viral core enters cytoplasm"]:::outcome E --> F["Reverse transcriptase synthesizes DNA<br/>using host dNTPs"]:::action F --> G["Integrase inserts provirus<br/>into host chromosome"]:::action G --> H["Host RNA Pol II transcribes<br/>viral genes"]:::action H --> I["Gag/Gag-Pol polyproteins synthesized"]:::outcome I --> J["Protease cleaves polyproteins<br/>during budding"]:::action J --> K["Mature infectious virions released"]:::outcome ``` **Key Point:** Every step depends on host cell machinery — there is no stage where HIV operates independently. [cite:Harrison 21e Ch 197]